Ketanserin Stabilizes Blood Pressure in Conscious Spontaneously Hypertensive Rats

1. It has been demonstrated that blood pressure variability (BPV) is increased in hypertension and related to organ damage. It will be important to lower BPV in the treatment of hypertension. The present study was designed to investigate the effect of ketanserin, a 5-HT2A receptor antagonist with a weak alpha1-adrenoceptor blocking effect, on BPV in conscious spontaneously hypertensive rats (SHR). 2. It was found that ketanserin decreased blood pressure (BP) and BPV in SHR when administered intravenously (3 mg/kg, i.v.). Ketanserin decreased BPV, but not the BP level, when administered intracerebroventricularly (50 microg/rat, i.c.v.). 3. Prazosin, an alpha1-adrenoceptor antagonist, lowered BP but did not affect BPV when given either i.v. (0.5 mg/kg) or i.c.v. (30 microg/rat). Ritanserin (0.625 mg/kg, i.v.; 40 microg/rat, i.c.v.), a 5-HT2A receptor antagonist, decreased BPV only when administered i.c.v. and did not modify the BP level. 4. Ketanserin enhanced arterial baroreflex function in SHR when given either i.v. or i.c.v. 5. The stabilizing effect of ketanserin on BP was persistent when administered intragastrically. This administration route is similar to oral administration clinically. 6. It is concluded that ketanserin is an antihypertensive agent with an effect of reducing BPV. This effect is mainly mediated by central 5-HT2A receptors and is probably attributable to the restoration of arterial baroreflex function.